During the past years we have been attempting to develop an efficient and non-toxic vector for gene transfer. Last year we reported that AKR murine leukemia viral (MuLV) genome could be stably transferred to uninfected recipient cells via isolated metaphase chromosomes. Although AKR virions are not able to infect heterologous cells, chromosome-mediated transfection resulted in the establishment of productive AKR MuLV infection in mink cells, which is not its normal host. Thus, the use of chromosomes to transfer virus genes can circumvent the natural host restriction barrier. Additionally, the carrier potential of liposomes for the transfer of simian virus 40 (SV40) DNA into mammalian cells has been investigated. It was found that the amount of DNA entrapped was dependent on the input DNA concentration and lipid composition of the liposomes. DNA remained intact after lipososme encapsulation and was resistant to deoxyribonuclease digestion. Negatively charged liposomes containing phosphatidylserine were more effective in DNA transfer and expression than neutral lipososmes. Lipososme entrapped SV40 minichromosomes were 20 fold more infective than the free minichromosomes, but only 20% more infective than liposome entrapped SV40 DNA. These data suggest that liposomes are suitable carriers for introduction of exogeneous DNA (eg. SV 40 DNA) and chromatin into mammalian cells in culture.